Angiotensin converting enzyme (ACE) is one of a class of zinc metallopeptidases that catalyze the cleavage of dipeptides from the C-terminal of oligopeptides and proteins. The enzyme from lung plays a central role in blood pressure regulation and lately much attention has been given to the design and use of ACE inhibitors as antihypertensive agents. The enzyme is also present in other tissues where its biological role is unknown. We have recently developed an affinity chromatographic method for ACE that allows us to obtain the enzyme conveniently, in quantities sufficient for physicochemical characterization. We plan to investigate the structural basis for chloride activation, the role of zinc and tyrosine in catalysis, enzymatic reaction intermediates and the putative endopeptidase activity of ACE. We will also examine the dipeptidyl carboxypeptidase from tissues other than lung - expecially testes, heart and brain - and from different species. By identifying physiological substrates for these enzymes we should be able to define their role in processing biologically active peptides.